Journal
ONCOTARGET
Volume 8, Issue 15, Pages 24644-24651Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.15602
Keywords
cholangiocarcinoma; PD-1; PD-L1; immunotherapy
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Cholangiocarcinoma is an aggressive biliary neoplasm lacking effective therapeutic agents. Immunotherapies targeting the PD-L1/PD-1 immune checkpoint have shown encouraging results in solid and hematologic cancers in clinical trials. Response to these immunomodulators is correlated with PD-L1 expression. Our goal was to characterize PD-L1 expression in intra-hepatic (iCCA) and perihilar (pCCA) cholangiocarcinomas, and to correlate our results with clinicopathological features, density of tumor-infiltrating lymphocytes (TILs) and PD-1 expression. A series of 58 iCCAs and 41 pCCAs was included in the study. PD-L1, PD-1 and CD3 expression was investigated using immunohistochemistry. Density of TILs was evaluated by immunohistochemistry using a quantitative score of CD3-stained intratumoral lymphocytes. PD-L1 expression by neoplastic cells was observed in 9 cases (9%, 5 iCCAs and 4 pCCAs). PD-L1 positive inflammatory cell aggregates were identified in 46% (n = 46) of the cases (31 iCCAs and 15 pCCAs). PD-L1 expression by either neoplastic or inflammatory cells was associated to high density of CD3-positive TILs (p = 0.01 and p = 0.005, respectively). The number of PD-L1 positive inflammatory cell aggregates was higher in tumors with high PD-1 expression (p < 0.0001). Altogether, PD-L1 in iCCA and pCCA is mainly expressed in tumors with high density of TILs. Our results suggest that CCAs with dense intratumoral lymphocytic infiltration might represent good candidates for PD-L1/PD-1 blocking agents.
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